This COVID treatment is almost useless against Omicron BA.2. Why is Canada still using it?

Content item

“Goodbye to #Sotrovimab. We hardly knew you,” University of Minnesota infectious diseases doctor David Boulware tweeted this week after America’s drug regulator limited access to the COVID antibody therapy, of which Canada has purchased 30,000 doses.

Content item

Emerging data from test tube experiments suggest the pricey, lab-made monoclonal antibody therapy has lost its potency against BA.2, the Omicron subvariant now spreading across Canada.

Ontario’s COVID-19 scientific advisers decided late Tuesday night to recommend doctors stop using the drug, period. But while Health Canada said it is aware of sotrovimab’s “limited efficacy” against BA.2, the agency is awaiting more data from drug maker GlaxoSmithKline.

It’s the latest drug the pandemic virus has put a partial kibosh to. As Nature reported, researchers are struggling to keep up with SARS-CoV-2 as the virus evolves. “With monoclonal antibodies, we’re trying to hit a moving target,” virologist David Ho, at Columbia University in New York City, told the journal.

Content item

Monoclonal antibody therapy—lab-made molecules that attach to the spike protein the virus uses to invade human cells—can help reduce the risk of COVID progressing from mild, to severe. It’s given only to people at high risk of being hospitalized or dying due to COVID because of their age or medical conditions.

At $2,100 per treatment course, sotrovimab is the only remaining available monoclonal antibody treatment in Canada shown to work against BA.1, the original form of Omicron. While BA.1 out muscled two other antibody treatments made by Eli Lilly and Regeneron, it’s still sensitive to sotrovimab. However, lab experiments have revealed a dramatic drop in the drug’s ability to neutralize BA.2.

“It’s hard to know exactly how much, but it’s somewhere between 30 to 45 times less able to neutralize (BA.2) than normally,” said Dr. Andrew Morris, an infectious diseases doctor and co-chair of Ontario’s drugs and biologics clinical practice guidelines working group.

Content item

Australian researchers also recently reported that the drug appears capable of causing treatment-resistant mutations in a small number of people.

“For those two reasons, it does not make sense to give it to patients when BA.2 has become the dominant strain through most of Canada,” Morris said. With testing limited, there’s no rapid way of determining who has BA.1 versus BA.2, and the probability of people being infected with BA.2 is only increasing.

The US Food and Drug Administration has paused use of the drug across New York, New Jersey and eight other states or territories where BA.2 accounts for more than 50 per cent of confirmed COVID-19 infections. GSK said it is preparing to submit data supporting a higher dose of its drug for Omicron BA.2, and will be sharing the data with health regulators globally, including Health Canada.

Content item

Once that data is assessed, “the department will communicate the information on our web portal as well as with health-care professionals,” Health Canada said. “Health-care professionals are responsible for making decisions with regard to the best treatment options for their patients considering the local epidemiological context.”

The intravenous drug remdesivir and two anti-COVID-19 pills, Pfizer’s Paxlovid and Merck’s molnupiravir, remained effective against BA.2 in laboratory tests, according to new research.

With SARS-Cov-2, the evolutionary changes have been much more rapid than researchers anticipated, Morris said. One monoclonal antibody therapy now available in the US appears effective against BA.2. “I haven’t seen evidence of even a submission to Health Canada,” said Morris, a professor of medicine at the University of Toronto.

Content item

“They’ve been burned twice now with purchasing large amounts and not able to utilize much of it.”

Monoclonal antibodies bind to the spike protein. It’s like a glove fitting on a hand, Morris said. “The problem is the hand keeps changing. It needs to be a good fit.” Every time the protein undergoes multiple changes, or hyper mutates, it can be enough to render the monoclonals inactive.

Montreal infectious diseases specialist Dr. Matthew Oughton said results in a test tube don’t always perfectly correlate with results in a human. “We don’t yet know whether this will result in clinical failure. It certainly raises the question. But that’s a big step away from being able to say, unquestionably, that sotrovimab has no effect.”

He wasn’t aware of any official guidance to Quebec doctors as of Wednesday morning. However, “if you ask me based on the available data we have, I think it’s a very good thing to be questioning whether we should at least pause on this,” said Oughton, a physician with Montreal’s Jewish General Hospital.

Two months ago it would have been a riskier decision to make. With increasing supplies of Paxlovid, Pfizer’s oral anti-COVID pill, “we have at least something we can reliably turn to,” he said.

National Post